Summary (Project 2: How olfactory information is transformed from bulb to cortex) Understanding how sensation is transformed into perception is a central challenge for neuroscience. Sensory information is detected by receptors that interact with the external world. This information is then routed, through multiple stages of processing, to cortical sensory areas, where perception first emerges. In this project we take advantage of the relatively ?shallow? organization of the rodent olfactory system to determine how odor infor- mation is directly transformed from olfactory bulb to piriform cortex; essentially, examining the transformation of sensory representations of the olfactory input in the bulb to cortical representations of the olfactory percept within a single stage of processing. To do this, we will combine the technical expertise of the Franks Lab (Duke Uni- versity) at recording and analyzing activity of large populations of piriform neurons, with the expertise of Rinberg Lab (New York University) at patterned optogenetic activation of olfactory bulb glomeruli. Combining our efforts provides us the unique opportunity to directly activate defined areas of olfactory bulb (i.e. Input) while recording from populations of neurons in piriform cortex (i.e. Output). This provides a unique opportunity to directly and systematically determine how olfactory information is transformed from an elemental sensory representation in bulb into a holistic perceptual representation in cortex. We will then use a variety of molecular genetic tools to selectively disrupt specific components of this circuit, which will reveal the distinct cellular operations that each component plays in implementing this transformation. This project will therefore provide deep mechanistic insight into how the brain transforms olfactory sensory information into cortical odor percepts. Thus, we are confident that we will reveal the logic of the transformation of olfactory information from bulb to cortex However, the logic and implementation of the bulb-to-piriform transformation is also likely to be instantiated at multiple other sites throughout the brain, and often at sites that are deeply embedded within the brain, such as the hippocampus, where access to both the Input and Output are more challenging, and so operations performed at these deeper areas are more difficult to interpret. We are therefore optimistic that lessons learned while probing our olfactory circuit will generate generalizable principles that will also apply to multiple other, similarly organized systems.